Exposure to high altitude induces pulmonary hypertension that may lead to life-threatening conditions. In a randomized, double-blind, placebo-controlled study, the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects were examined. Twelve subjects (sildenafil [SIL] n = 6; placebo [PLA] n = 6) were exposed for 6 days at 4,350 m. Treatment (3 x 40 mg/day) was started 6 to 8 hours after arrival from sea level to high altitude and maintained for 6 days. Systolic pulmonary artery pressure (echocardiography) increased at high altitude before treatment (+29% versus sea level, p < 0.01), then normalized in SIL (-6% versus sea level, NS) and remained elevated in PLA (+21% versus sea level, p < 0.05). Pulmonary acceleration time decreased by 27% in PLA versus 6% in SIL (p < 0.01). Cardiac output and systemic blood pressures increased at high altitude then decreased similarly in both groups. Pa(O(2)) was higher and alveolar-arterial difference in O(2) lower in SIL than in PLA at rest and exercise (p < 0.05). The altitude-induced decrease in maximal O(2) consumption was smaller in SIL than in PLA (p < 0.05). Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise performance.

The factors determining maximal oxygen consumption were explored in eight endurance trained subjects (TS) and eight untrained subjects (US) exposed to moderate acute normobaric hypoxia. Subjects performed maximal incremental tests at sea level and simulated altitudes (1,000, 2,500, 4,500 m). Heart rate (HR), stroke volume (SV), cardiac output (.Q), arterialized oxygen saturation (Sa'O2), oxygen uptake (.VO2max), ventilation (.VE, expressed in normobaric conditions) were measured. At maximal exercise, ventilatory equivalent (.VE/.VO2max), O2 transport (.QaO2max) and O2 extraction (O2ERmax) were calculated. In TS, .Qmax remained unchanged despite a significant reduction in HRmax at 4,500 m. SVmax remained unchanged. .VEmax decreased in TS at 4,500 m, .VE/.VO2max was lower in TS and greater at 4,500 m vs. sea level in both groups. Sa'O2max decreased at and above 1,000 m in TS and 2,500 m in US, O2ERmax increased at 4,500 m in both groups. .QaO2max decreased with altitude and was greater in TS than US up to 2,500 m but not at 4,500 m. .VO2max decreased with altitude but the decrement (Delta.VO2max) was larger in TS at 4,500 m. In both groups Delta.VO2max in moderate hypoxia was correlated with Delta.QaO2max. Several differences between the two groups are probably responsible for the greater Delta.VO2max in TS at 4,500 m : (1) the relative hypoventilation in TS as shown by the decrement in .VEmax at 4,500 m (2) the greater.QaO2max decrement in TS due to a lower Sa'O2max and unchanged .Qmax 3) the smaller increase in O2ERmax in TS, insufficient to compensate the decrease in .QaO2max.

Both acute hypoxia and sildenafil may influence autonomic control through transient cardiovascular effects. In a double-blind study, we investigated whether sildenalfil (Sil) could interfere with cardiovascular effects of hypoxia. Twelve healthy men [placebo (Pla) n = 6; Sil, n = 6] were exposed to an altitude of 4,350 m during 6 days. Treatment was continuously administered from 6 to 8 h after arrival at altitude (3 x 40 mg/day). The autonomic control on the heart was assessed by heart rate variability (HRV) during sleep at sea level (SL) and between day 1-2 and day 5-6 in hypoxia. Arterial pressure (AP) and total peripheral resistances (TPR) were obtained during daytime. There was no statistical difference between groups in HRV, AP, and TPR throughout the study. Hypoxia induced a decrease in R-R interval and an increase in AP in both groups. Low frequency-to-high frequency ratio increased at day 1-2 (Pla, P = 0.04; Sil, P = 0.02) and day 5-6 (Pla and Sil, P = 0.04) vs. SL, whereas normalized high-frequency power decreased only in Pla (P = 0.04, day 1-2 vs. SL). Normalized low-frequency power increased at high altitude (Pla and Sil, P = 0.04, day 5-6 vs. SL). TPR decreased at day 2 in Pla (P = 0.02) and tended to normalize at day 6 (P = 0.07, day 6 vs. day 2). Acute hypoxia induced a decrease in parasympathetic and increase in sympathetic tone, which tended to be reversed with acclimatization. Sil had no deleterious effects on the cardiovascular response to high-altitude exposure and its control by the autonomic nervous system.

These results demonstrate that endurance-trained women show a greater decrement in VO(2max) at high altitudes. This could be explained mainly by a higher arterial desaturation, which is largely caused, according to our results, by diffusion limitation.

Eight men performed three series of 5-min exercise on a cycle ergometer at 65% of normoxic maximal O(2) consumption in four conditions: (1) voluntary hypoventilation (VH) in normoxia (VH(0.21)), (2) VH in hyperoxia (inducing hypercapnia) (inspired oxygen fraction [F(I)O(2)] = 0.29; VH(0.29)), (3) normal breathing (NB) in hypoxia (F(I)O(2) = 0.157; NB(0.157)), (4) NB in normoxia (NB(0.21)). Using near-infrared spectroscopy, changes in concentration of oxy-(Delta[O(2)Hb]) and deoxyhemoglobin (Delta[HHb]) were measured in the vastus lateralis muscle. Delta[O(2)Hb - HHb] and Delta[O(2)Hb + HHb] were calculated and used as oxygenation index and change in regional blood volume, respectively. Earlobe blood samples were taken throughout the exercise. Both VH(0.21) and NB(0.157) induced a severe and similar hypoxemia (arterial oxygen saturation [SaO(2)] < 88%) whereas SaO(2) remained above 94% and was not different between VH(0.29) and NB(0.21). Arterialized O(2) and CO(2) pressures as well as P50 were higher and pH lower in VH(0.21) than in NB(0.157), and in VH(0.29) than in NB(0.21). Delta[O(2)Hb] and Delta[O(2)Hb - HHb] were lower and Delta[HHb] higher at the end of each series in both VH(0.21) and NB(0.157) than in NB(0.21) and VH(0.29). There was no difference in Delta[O(2)Hb + HHb] between testing conditions. [La] in VH(0.21) was greater than both in NB(0.21) and VH(0.29) but not different from NB(0.157). This study demonstrated that exercise with VH induced a lower tissue oxygenation and a higher [La] than exercise with NB. This was caused by a severe arterial O(2) desaturation induced by both hypoxic and hypercapnic effects.